JP2003517429A - アロステリックアデノシン受容体修飾物質 - Google Patents
アロステリックアデノシン受容体修飾物質Info
- Publication number
- JP2003517429A JP2003517429A JP2000517772A JP2000517772A JP2003517429A JP 2003517429 A JP2003517429 A JP 2003517429A JP 2000517772 A JP2000517772 A JP 2000517772A JP 2000517772 A JP2000517772 A JP 2000517772A JP 2003517429 A JP2003517429 A JP 2003517429A
- Authority
- JP
- Japan
- Prior art keywords
- amino
- pyridine
- tetrahydrothieno
- benzoyl
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108050000203 Adenosine receptors Proteins 0.000 title claims abstract description 13
- 102000009346 Adenosine receptors Human genes 0.000 title claims abstract description 13
- 230000003281 allosteric effect Effects 0.000 title abstract description 16
- 229940075993 receptor modulator Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 194
- 238000000034 method Methods 0.000 claims abstract description 55
- 230000004224 protection Effects 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims description 74
- 150000002431 hydrogen Chemical class 0.000 claims description 56
- -1 amino-protected amino Chemical group 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 36
- 239000000126 substance Substances 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 239000000460 chlorine Substances 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- CQQSPRAGMLYQRC-UHFFFAOYSA-N (2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-phenylmethanone Chemical compound NC=1SC=2CNCCC=2C=1C(=O)C1=CC=CC=C1 CQQSPRAGMLYQRC-UHFFFAOYSA-N 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000000539 amino acid group Chemical group 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004450 alkenylene group Chemical group 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 7
- LMSVMYYPOYHGMJ-UHFFFAOYSA-N (2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(4-chlorophenyl)methanone Chemical compound NC=1SC=2CNCCC=2C=1C(=O)C1=CC=C(Cl)C=C1 LMSVMYYPOYHGMJ-UHFFFAOYSA-N 0.000 claims description 6
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 125000005179 haloacetyl group Chemical group 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 230000036407 pain Effects 0.000 claims description 6
- MOSJYUMNKDWKIJ-UHFFFAOYSA-N (2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(4-phenylphenyl)methanone Chemical compound NC=1SC=2CNCCC=2C=1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 MOSJYUMNKDWKIJ-UHFFFAOYSA-N 0.000 claims description 5
- 125000006418 4-methylphenylsulfonyl group Chemical group 0.000 claims description 5
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 150000001450 anions Chemical class 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- SPEVULGDXPQWLD-UHFFFAOYSA-N (2-amino-2h-cyclopenta[b]thiophen-3-yl)-(4-bromophenyl)methanone Chemical compound NC1SC2=CC=CC2=C1C(=O)C1=CC=C(Br)C=C1 SPEVULGDXPQWLD-UHFFFAOYSA-N 0.000 claims description 4
- GTNDJYARMHNXMS-UHFFFAOYSA-N (2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(4-iodophenyl)methanone Chemical compound NC=1SC=2CNCCC=2C=1C(=O)C1=CC=C(I)C=C1 GTNDJYARMHNXMS-UHFFFAOYSA-N 0.000 claims description 4
- HFLMHMGIVXQGIB-UHFFFAOYSA-N (2-aminothiophen-3-yl)-(4-chlorophenyl)methanone Chemical compound S1C=CC(C(=O)C=2C=CC(Cl)=CC=2)=C1N HFLMHMGIVXQGIB-UHFFFAOYSA-N 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 208000010412 Glaucoma Diseases 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- XDGTWWIUDGYOPC-UHFFFAOYSA-N [1]benzothiolo[2,3-b]pyridine Chemical compound C1=CC=C2C3=CC=CC=C3SC2=N1 XDGTWWIUDGYOPC-UHFFFAOYSA-N 0.000 claims description 4
- JWFMHRCZOVTSKI-UHFFFAOYSA-N [2-amino-6,6-bis(3-methylbut-2-enyl)-5,7-dihydro-4h-thieno[2,3-c]pyridin-6-ium-3-yl]-(4-phenylphenyl)methanone;chloride Chemical compound [Cl-].C1[N+](CC=C(C)C)(CC=C(C)C)CCC2=C1SC(N)=C2C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 JWFMHRCZOVTSKI-UHFFFAOYSA-N 0.000 claims description 4
- CYGQGIRXYHGLBY-UHFFFAOYSA-N [2-amino-6-(3-methylbut-2-enyl)-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl]-(4-bromophenyl)methanone Chemical compound C1N(CC=C(C)C)CCC2=C1SC(N)=C2C(=O)C1=CC=C(Br)C=C1 CYGQGIRXYHGLBY-UHFFFAOYSA-N 0.000 claims description 4
- BSTAFQRRZHHFTQ-UHFFFAOYSA-N [2-amino-6-(3-methylbut-2-enyl)-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl]-(4-chlorophenyl)methanone Chemical compound C1N(CC=C(C)C)CCC2=C1SC(N)=C2C(=O)C1=CC=C(Cl)C=C1 BSTAFQRRZHHFTQ-UHFFFAOYSA-N 0.000 claims description 4
- KFMLWKYJGFGILS-UHFFFAOYSA-N [2-amino-6-[2-(4-nitrophenyl)ethyl]-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl]-(4-chlorophenyl)methanone Chemical compound C1CC=2C(C(=O)C=3C=CC(Cl)=CC=3)=C(N)SC=2CN1CCC1=CC=C([N+]([O-])=O)C=C1 KFMLWKYJGFGILS-UHFFFAOYSA-N 0.000 claims description 4
- 238000002399 angioplasty Methods 0.000 claims description 4
- GULCAVRIFKAGBA-UHFFFAOYSA-N benzyl 2-amino-3-(4-chlorobenzoyl)-5,7-dihydro-4h-thieno[2,3-c]pyridine-6-carboxylate Chemical compound NC=1SC=2CN(C(=O)OCC=3C=CC=CC=3)CCC=2C=1C(=O)C1=CC=C(Cl)C=C1 GULCAVRIFKAGBA-UHFFFAOYSA-N 0.000 claims description 4
- SWMIKGPXARWYGZ-UHFFFAOYSA-N benzyl 2-amino-3-benzoyl-5,7-dihydro-4h-thieno[2,3-c]pyridine-6-carboxylate Chemical compound NC=1SC=2CN(C(=O)OCC=3C=CC=CC=3)CCC=2C=1C(=O)C1=CC=CC=C1 SWMIKGPXARWYGZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 230000000747 cardiac effect Effects 0.000 claims description 4
- 238000012875 competitive assay Methods 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 4
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 4
- 208000019116 sleep disease Diseases 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 206010021639 Incontinence Diseases 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 235000021588 free fatty acids Nutrition 0.000 claims description 3
- 150000002466 imines Chemical class 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 230000035945 sensitivity Effects 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
- 206010012735 Diarrhoea Diseases 0.000 claims description 2
- 102000004877 Insulin Human genes 0.000 claims description 2
- 108090001061 Insulin Proteins 0.000 claims description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 2
- 208000003734 Supraventricular Tachycardia Diseases 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 229940125396 insulin Drugs 0.000 claims description 2
- 230000007774 longterm Effects 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 150000003626 triacylglycerols Chemical class 0.000 claims description 2
- 230000005961 cardioprotection Effects 0.000 claims 4
- QJCQJXOEXKINTC-UHFFFAOYSA-N (2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)-phenylmethanone Chemical compound NC=1SC=2CCCCC=2C=1C(=O)C1=CC=CC=C1 QJCQJXOEXKINTC-UHFFFAOYSA-N 0.000 claims 3
- XASIBOPNKNSCSE-UHFFFAOYSA-N (2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(4-bromophenyl)methanone Chemical compound NC=1SC=2CNCCC=2C=1C(=O)C1=CC=C(Br)C=C1 XASIBOPNKNSCSE-UHFFFAOYSA-N 0.000 claims 3
- LUEXTQZEWNFRIZ-UHFFFAOYSA-N (2-amino-6-benzyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl)-(4-chlorophenyl)methanone Chemical compound C1CC=2C(C(=O)C=3C=CC(Cl)=CC=3)=C(N)SC=2CN1CC1=CC=CC=C1 LUEXTQZEWNFRIZ-UHFFFAOYSA-N 0.000 claims 3
- YECOLIOURFRXLE-UHFFFAOYSA-N (2-amino-6-benzyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl)-[3-(trifluoromethyl)phenyl]methanone Chemical compound C1CC=2C(C(=O)C=3C=C(C=CC=3)C(F)(F)F)=C(N)SC=2CN1CC1=CC=CC=C1 YECOLIOURFRXLE-UHFFFAOYSA-N 0.000 claims 3
- OMPLSIJAEKIZMC-UHFFFAOYSA-N (2-amino-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl)-phenylmethanone Chemical compound C1N(C)CCC2=C1SC(N)=C2C(=O)C1=CC=CC=C1 OMPLSIJAEKIZMC-UHFFFAOYSA-N 0.000 claims 3
- VFDPRGAJPQIMRK-UHFFFAOYSA-N (2-amino-6-prop-2-enyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl)-(4-bromophenyl)methanone Chemical compound NC=1SC=2CN(CC=C)CCC=2C=1C(=O)C1=CC=C(Br)C=C1 VFDPRGAJPQIMRK-UHFFFAOYSA-N 0.000 claims 3
- JEHXJTDSXYWRHI-UHFFFAOYSA-N (2-amino-6-prop-2-enyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl)-(4-chlorophenyl)methanone Chemical compound NC=1SC=2CN(CC=C)CCC=2C=1C(=O)C1=CC=C(Cl)C=C1 JEHXJTDSXYWRHI-UHFFFAOYSA-N 0.000 claims 3
- ZBDLPPZGLLXINX-UHFFFAOYSA-N 2-amino-3-(4-bromobenzoyl)-n-phenyl-5,7-dihydro-4h-thieno[2,3-c]pyridine-6-carboxamide Chemical compound NC=1SC=2CN(C(=O)NC=3C=CC=CC=3)CCC=2C=1C(=O)C1=CC=C(Br)C=C1 ZBDLPPZGLLXINX-UHFFFAOYSA-N 0.000 claims 3
- ICNLKPSOZILBBU-UHFFFAOYSA-N 2-amino-3-(4-chlorobenzoyl)-n-phenyl-5,7-dihydro-4h-thieno[2,3-c]pyridine-6-carboxamide Chemical compound NC=1SC=2CN(C(=O)NC=3C=CC=CC=3)CCC=2C=1C(=O)C1=CC=C(Cl)C=C1 ICNLKPSOZILBBU-UHFFFAOYSA-N 0.000 claims 3
- UFTCMHVQWNMEHE-UHFFFAOYSA-N 2-amino-3-(4-iodobenzoyl)-n-phenyl-5,7-dihydro-4h-thieno[2,3-c]pyridine-6-carboxamide Chemical compound NC=1SC=2CN(C(=O)NC=3C=CC=CC=3)CCC=2C=1C(=O)C1=CC=C(I)C=C1 UFTCMHVQWNMEHE-UHFFFAOYSA-N 0.000 claims 3
- GXSMFBBCYCENEC-UHFFFAOYSA-N 2-amino-4-phenyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-b]pyridine-3-carbonitrile Chemical compound N#CC=1C(N)=NC=2SC=3CCCCC=3C=2C=1C1=CC=CC=C1 GXSMFBBCYCENEC-UHFFFAOYSA-N 0.000 claims 3
- 125000002981 3-(trifluoromethyl)benzoyl group Chemical group FC(C=1C=C(C(=O)*)C=CC1)(F)F 0.000 claims 3
- TYHGPCYYNZWXKO-UHFFFAOYSA-N 4-phenyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine Chemical compound C1CCCC(C=23)=C1SC3=NC=NC=2C1=CC=CC=C1 TYHGPCYYNZWXKO-UHFFFAOYSA-N 0.000 claims 3
- WXJGGNWYYNMMEJ-UHFFFAOYSA-N CC(=CCC1=CC2=C(S1)CNCC2)C Chemical compound CC(=CCC1=CC2=C(S1)CNCC2)C WXJGGNWYYNMMEJ-UHFFFAOYSA-N 0.000 claims 3
- VMIQRWAFDLFQEJ-UHFFFAOYSA-N [2-amino-6-(2-phenylethyl)-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl]-(4-chlorophenyl)methanone Chemical compound C1CC=2C(C(=O)C=3C=CC(Cl)=CC=3)=C(N)SC=2CN1CCC1=CC=CC=C1 VMIQRWAFDLFQEJ-UHFFFAOYSA-N 0.000 claims 3
- VAOQLVBIABOKRH-UHFFFAOYSA-N [2-amino-6-(2-phenylethyl)-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl]-[3-(fluoromethyl)phenyl]methanone Chemical compound C1CC=2C(C(=O)C=3C=C(CF)C=CC=3)=C(N)SC=2CN1CCC1=CC=CC=C1 VAOQLVBIABOKRH-UHFFFAOYSA-N 0.000 claims 3
- CZUHTJPPXSSLIB-UHFFFAOYSA-N [2-amino-6-(3-methylbut-2-enyl)-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl]-phenylmethanone Chemical compound C1N(CC=C(C)C)CCC2=C1SC(N)=C2C(=O)C1=CC=CC=C1 CZUHTJPPXSSLIB-UHFFFAOYSA-N 0.000 claims 3
- XQVYRFCAMRPJQW-UHFFFAOYSA-N [2-amino-6-(4-methylphenyl)sulfonyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl]-phenylmethanone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC(SC(N)=C2C(=O)C=3C=CC=CC=3)=C2CC1 XQVYRFCAMRPJQW-UHFFFAOYSA-N 0.000 claims 3
- LPDXACNTICXBPM-UHFFFAOYSA-N [2-amino-6-[2-(4-nitrophenyl)ethyl]-5,7-dihydro-4h-thieno[2,3-c]pyridin-3-yl]-phenylmethanone Chemical compound C1CC=2C(C(=O)C=3C=CC=CC=3)=C(N)SC=2CN1CCC1=CC=C([N+]([O-])=O)C=C1 LPDXACNTICXBPM-UHFFFAOYSA-N 0.000 claims 3
- FDOKFNOHDQGWHZ-UHFFFAOYSA-N benzyl 2-amino-3-(4-fluorobenzoyl)-5,7-dihydro-4h-thieno[2,3-c]pyridine-6-carboxylate Chemical compound NC=1SC=2CN(C(=O)OCC=3C=CC=CC=3)CCC=2C=1C(=O)C1=CC=C(F)C=C1 FDOKFNOHDQGWHZ-UHFFFAOYSA-N 0.000 claims 3
- GAOXTEDKYOARFC-UHFFFAOYSA-N benzyl 2-amino-3-(4-phenylbenzoyl)-5,7-dihydro-4h-thieno[2,3-c]pyridine-6-carboxylate Chemical compound NC=1SC=2CN(C(=O)OCC=3C=CC=CC=3)CCC=2C=1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 GAOXTEDKYOARFC-UHFFFAOYSA-N 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- ZUAYYFLMNWCTOG-UHFFFAOYSA-N ethyl 2-(2-amino-3-benzoyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-6-yl)acetate Chemical compound C1N(CC(=O)OCC)CCC2=C1SC(N)=C2C(=O)C1=CC=CC=C1 ZUAYYFLMNWCTOG-UHFFFAOYSA-N 0.000 claims 3
- MFBXKDKZGFIBNE-UHFFFAOYSA-N ethyl 2-[2-amino-3-(4-chlorobenzoyl)-5,7-dihydro-4h-thieno[2,3-c]pyridin-6-yl]acetate Chemical compound C1N(CC(=O)OCC)CCC2=C1SC(N)=C2C(=O)C1=CC=C(Cl)C=C1 MFBXKDKZGFIBNE-UHFFFAOYSA-N 0.000 claims 3
- YPMDNTUIBGXTFO-UHFFFAOYSA-N ethyl 2-methyl-4-phenyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-b]pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)N=C2SC=3CCCCC=3C2=C1C1=CC=CC=C1 YPMDNTUIBGXTFO-UHFFFAOYSA-N 0.000 claims 3
- 210000000653 nervous system Anatomy 0.000 claims 3
- 238000010253 intravenous injection Methods 0.000 claims 2
- 230000005923 long-lasting effect Effects 0.000 claims 2
- 241001024304 Mino Species 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 claims 1
- 238000007675 cardiac surgery Methods 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 230000029537 positive regulation of insulin secretion Effects 0.000 claims 1
- 208000020685 sleep-wake disease Diseases 0.000 claims 1
- 230000009861 stroke prevention Effects 0.000 claims 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
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Classifications
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- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/66—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/959,758 US5939432A (en) | 1997-10-29 | 1997-10-29 | Thiophenes useful for modulating the adenosine receptor |
| US08/959,758 | 1997-10-29 | ||
| US09/156,077 US6323214B1 (en) | 1997-10-29 | 1998-09-17 | Allosteric adenosine receptor modulators |
| US09/156,077 | 1998-09-17 | ||
| PCT/US1998/020333 WO1999021617A2 (en) | 1997-10-29 | 1998-09-30 | Allosteric adenosine receptor modulators |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004225107A Division JP2005002129A (ja) | 1997-10-29 | 2004-08-02 | アロステリックアデノシン受容体修飾物質 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003517429A true JP2003517429A (ja) | 2003-05-27 |
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| JP2000517772A Pending JP2003517429A (ja) | 1997-10-29 | 1998-09-30 | アロステリックアデノシン受容体修飾物質 |
| JP2004225107A Pending JP2005002129A (ja) | 1997-10-29 | 2004-08-02 | アロステリックアデノシン受容体修飾物質 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2004225107A Pending JP2005002129A (ja) | 1997-10-29 | 2004-08-02 | アロステリックアデノシン受容体修飾物質 |
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| Country | Link |
|---|---|
| US (3) | US5939432A (enExample) |
| EP (1) | EP1025106B1 (enExample) |
| JP (2) | JP2003517429A (enExample) |
| AT (1) | ATE330959T1 (enExample) |
| AU (1) | AU9671798A (enExample) |
| CA (1) | CA2302396C (enExample) |
| WO (1) | WO1999021617A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006500313A (ja) * | 2001-12-12 | 2006-01-05 | エフ.ホフマン−ラ ロシュ アーゲー | アデノシン受容体モジュレーターとしてのベンゾチオフェン |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6727258B2 (en) * | 1997-10-29 | 2004-04-27 | King Pharmaceutical Research & Development, Inc. | Allosteric adenosine receptor modulators |
| DE19947154A1 (de) * | 1999-10-01 | 2001-10-04 | Bayer Ag | Substituierte 2-Thio-3,5-dicyano-4-aryl-6-aminopyridine und ihre Verwendung |
| JP4502435B2 (ja) * | 1999-11-30 | 2010-07-14 | 興和創薬株式会社 | 4,5,6,7−テトラヒドロチエノ〔2,3−c〕ピリジン系化合物 |
| JP4548882B2 (ja) * | 1999-11-30 | 2010-09-22 | 興和創薬株式会社 | 4,5,6,7−テトラヒドロチエノ〔2,3−c〕ピリジン化合物 |
| JP4548884B2 (ja) * | 1999-12-03 | 2010-09-22 | 興和創薬株式会社 | 4,5,6,7−テトラヒドロチエノ〔2,3−c〕ピリジン誘導体 |
| CA2414623A1 (en) * | 2000-08-01 | 2002-02-07 | University Of Virginia Patent Foundation | Use of selective adenosine a1 receptor agonists, antagonists and allosteric enhancers to manipulate angiogenesis |
| US6489356B2 (en) * | 2000-09-05 | 2002-12-03 | Edward Leung | Method for treating pain in humans |
| US6248774B1 (en) * | 2000-09-05 | 2001-06-19 | King Pharmaceuticals Research & Development, Inc. | Method for treating hyper-excited sensory nerve functions in humans |
| GB0100622D0 (en) | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds V111 |
| GB0100620D0 (en) * | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical cokpounds V |
| GB0100624D0 (en) * | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds VII |
| GB0100621D0 (en) * | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds VI |
| US20020115635A1 (en) * | 2001-02-21 | 2002-08-22 | Pnina Fishman | Modulation of GSK-3beta activity and its different uses |
| JP4303474B2 (ja) | 2001-03-30 | 2009-07-29 | キング・ファーマシューティカルズ・インコーポレイティッド | 医薬活性のある化合物及び使用方法 |
| US6713638B2 (en) * | 2001-05-18 | 2004-03-30 | Joel M. Linden | 2-amino-3-aroyl-4,5 alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors |
| EP1583530A4 (en) * | 2002-01-16 | 2008-07-23 | Univ Virginia | 2-AMINOTHIAZOLE ALLOSTERIC AMPLIFIERS OF A1 ADENOSINE RECEPTORS |
| US20040121406A1 (en) * | 2002-05-23 | 2004-06-24 | Wilson Constance Neely | Methods and formulations for increasing the affinity of a1 adenosine receptor ligands for the a1 adenosine receptor |
| EP1633756B1 (en) | 2003-04-09 | 2008-12-24 | Biogen Idec MA Inc. | A2a adenosine receptor antagonists |
| US7285550B2 (en) | 2003-04-09 | 2007-10-23 | Biogen Idec Ma Inc. | Triazolotriazines and pyrazolotriazines and methods of making and using the same |
| WO2004092177A1 (en) | 2003-04-09 | 2004-10-28 | Biogen Idec Ma Inc. | Triazolopyrazines and methods of making and using the same |
| US8062272B2 (en) * | 2004-05-21 | 2011-11-22 | Bluesky Medical Group Incorporated | Flexible reduced pressure treatment appliance |
| KR20090112627A (ko) * | 2006-11-13 | 2009-10-28 | 킹 파머슈티칼스 리서치 앤드 디벨로프먼트 아이엔씨 | 에이1 아데노신 수용체의 알로스테릭 조절제 |
| US7855209B2 (en) * | 2006-11-13 | 2010-12-21 | King Pharmaceuticals Research And Development, Inc. | Allosteric modulators of the A1 adenosine receptor |
| US7897596B2 (en) * | 2006-11-13 | 2011-03-01 | King Pharmaceuticals Research & Development, Inc. | Allosteric modulators of the A1 adenosine receptor |
| PA8801401A1 (es) * | 2007-10-25 | 2009-05-15 | Janssen Pharmaceutica Nv | Arilindenopirimidinas y su uso como adenosina a2a |
| GB0722340D0 (en) * | 2007-11-14 | 2007-12-27 | Univ Leiden | Sphingosine-1-phosphate (S1P) receptor compounds |
| US20090281145A1 (en) * | 2008-05-08 | 2009-11-12 | Pier Giovanni Baraldi | Allosteric enhancers of the a1 adenosine receptor |
| GB0906579D0 (en) | 2009-04-16 | 2009-05-20 | Vernalis R&D Ltd | Pharmaceuticals, compositions and methods of making and using the same |
| US20100093714A1 (en) * | 2008-10-13 | 2010-04-15 | Devraj Chakravarty | AMIDES OF THIENO[2,3-d]PYRIMIDINE AND THEIR USE AS ADENOSINE A2a RECEPTOR ANTAGONISTS |
| US20100093702A1 (en) * | 2008-10-13 | 2010-04-15 | Barbay J Kent | METHYLENE AMINES OF THIENO[2,3-d]PYRIMIDINE AND THEIR USE AS ADENOSINE A2a RECEPTOR ANTAGONISTS |
| US20100093763A1 (en) * | 2008-10-13 | 2010-04-15 | Barbay J Kent | PHENYL SUBSTITUTED THIENO[2,3-d]PYRIMIDINES AND THEIR USE AS ADENOSINE A2a RECEPTOR ANTAGONISTS |
| WO2011010306A1 (en) | 2009-07-21 | 2011-01-27 | Ramot At Tel-Aviv University Ltd. | A3 adenosine receptor ligands for modulation of pigmentation |
| CN113874015B (zh) | 2018-12-21 | 2024-05-24 | 细胞基因公司 | Ripk2的噻吩并吡啶抑制剂 |
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| CH540247A (de) * | 1967-04-21 | 1973-09-28 | Ciba Geigy Ag | Verfahren zur Herstellung von heterocyclischen, Asthylendoppelbindungen enthaltenden Verbindungen |
| ES393101A1 (es) * | 1971-07-09 | 1974-05-16 | Made Labor Sa | Procedimiento para la preparacion de derivados de tieno- diazepina. |
| FI54312C (fi) * | 1972-05-09 | 1978-11-10 | Sumitomo Chemical Co | Foerfarande foer framstaellning av tieno-(2,3-d)pyrimidinderivat med avsoendring av urinsyra i urin utoekande |
| JPS5342400B2 (enExample) | 1973-05-30 | 1978-11-10 | ||
| PH30676A (en) | 1986-07-22 | 1997-09-16 | Boehringer Ingelhein Kg | Hetrazepine compounds which have useful pharmaceutical utility |
| CH677511A5 (enExample) * | 1988-10-12 | 1991-05-31 | Mefina Sa | |
| US5026698A (en) | 1988-11-02 | 1991-06-25 | Nissan Chemical Industries, Ltd. | Thienopyridine type mevalonolactones |
| CA2020806A1 (en) * | 1989-07-12 | 1991-01-13 | Karl-Heinz Weber | Thienodiazepine derivatives |
| KR100255493B1 (ko) * | 1991-10-11 | 2000-08-01 | 가마쿠라 아키오 | 골조송증 치료제 |
| JPH05345785A (ja) * | 1992-01-16 | 1993-12-27 | Yoshitomi Pharmaceut Ind Ltd | トリアゾロオキサゼピン化合物 |
| TW263498B (enExample) * | 1993-11-10 | 1995-11-21 | Takeda Pharm Industry Co Ltd | |
| JPH07304755A (ja) * | 1994-05-12 | 1995-11-21 | Yamanouchi Pharmaceut Co Ltd | 縮合ジアゼピン誘導体 |
| FI971974L (fi) * | 1994-11-08 | 1997-06-18 | Takeda Chemical Industries Ltd | Tienopyridiini- tai tienopyrimidiinijohdannaiset ja niiden käyttö |
| US5585538A (en) | 1995-03-08 | 1996-12-17 | Pioneer Hi-Bred International, Inc. | Hybrid maize plant & seed (3936) |
| JPH08337583A (ja) * | 1995-04-13 | 1996-12-24 | Takeda Chem Ind Ltd | 複素環化合物およびその製造法 |
| US5757486A (en) * | 1996-11-22 | 1998-05-26 | Eastman Kodak Company | Digital camera image sensor positioning apparatus including a non-coherent light interferometer |
-
1997
- 1997-10-29 US US08/959,758 patent/US5939432A/en not_active Expired - Lifetime
-
1998
- 1998-09-30 WO PCT/US1998/020333 patent/WO1999021617A2/en not_active Ceased
- 1998-09-30 AT AT98950745T patent/ATE330959T1/de not_active IP Right Cessation
- 1998-09-30 CA CA002302396A patent/CA2302396C/en not_active Expired - Fee Related
- 1998-09-30 EP EP98950745A patent/EP1025106B1/en not_active Expired - Lifetime
- 1998-09-30 AU AU96717/98A patent/AU9671798A/en not_active Abandoned
- 1998-09-30 JP JP2000517772A patent/JP2003517429A/ja active Pending
-
1999
- 1999-05-07 US US09/307,225 patent/US6177444B1/en not_active Expired - Fee Related
- 1999-05-07 US US09/307,286 patent/US6194449B1/en not_active Expired - Fee Related
-
2004
- 2004-08-02 JP JP2004225107A patent/JP2005002129A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006500313A (ja) * | 2001-12-12 | 2006-01-05 | エフ.ホフマン−ラ ロシュ アーゲー | アデノシン受容体モジュレーターとしてのベンゾチオフェン |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2005002129A (ja) | 2005-01-06 |
| US6177444B1 (en) | 2001-01-23 |
| CA2302396A1 (en) | 1999-05-06 |
| WO1999021617A2 (en) | 1999-05-06 |
| WO1999021617A3 (en) | 1999-07-29 |
| AU9671798A (en) | 1999-05-17 |
| US6194449B1 (en) | 2001-02-27 |
| ATE330959T1 (de) | 2006-07-15 |
| US5939432A (en) | 1999-08-17 |
| WO1999021617B1 (en) | 1999-09-10 |
| EP1025106A2 (en) | 2000-08-09 |
| EP1025106B1 (en) | 2006-06-21 |
| CA2302396C (en) | 2002-06-04 |
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